Itch and pain are two fundamental sensory perceptions evoked by distinct external inputs. They are encoded and transmitted by primary nociceptive fibers and varying subpopulations of dorsal horn neurons. The ability to discriminate between itch and pain allows animals to employ the proper motor response (scratching vs. withdrawal) so that potentially damaging stimuli from the environment can be avoided. Intriguingly, it has been well documented that itch and pain may counteract each other under some conditions. Indeed, a wide range of noxious stimuli including thermal, mechanical, chemical and electrical stimuli are able to inhibit itch. Conversely, it is widely assumed that itch may be unmasked by pain reduction, and one of the most cited examples of this antagonistic relationship is opioid-induced itch, or pruritus. In fact, pruritus is one of the most prevalent acute side effects of the spinal or epidural use of opioids in patients who undergo pain treatment or in those who receive cesarean section, which has hampered the use of opioids as an analgesic to their full extent. Current treatment is to use antagonists against the μ opioid receptor, which also affects opioid analgesia. There is a need in the art, therefore, to separate opioid analgesia and opioid itch to treat opioid itch without compromising opioid analgesia.